DNA adducts in mouse testis and lung after inhalation exposure to 1,3-butadiene.
1,3-Butadiene is a widely used industrial chemical and also an environmental contaminant. Recent findings have shown that butadiene can also be a male germ cell mutagen. In this study, DNA adduct formation in testis and lung has been explored by using N7-alkylated guanines as a marker of biological effective dose. The adducts measured were the four structurally different guanine N7-adducts alkylated by butadienemonoepoxide, the main metabolite of 1,3-butadiene. This study demonstrates the dose-dependent adduct formation in lung and testis. At lower exposures (50 and 200 ppm) the adduct levels were about the same in the two organs, but at 500 ppm the adduct level was significantly (p < 0.03) higher in testis than in lung. The enantiomeric composition of the adducts detected was also different. In lung, all 4 possible adducts were present (S-C-1" dominating, 49%), but in testis only two out of four adducts were detected (S-C-2" being the most abundant adduct, 71%). These novel observations indicate that the DNA repair is different in these two organs studied and that heritable genetic effects observed may be mediated through the DNA adducts.
Koivisto
P
P
Molecular Dosimetry Group, Finnish Institute of Occupational Health, Helsinki, Finland.
Adler
I D
ID
Pacchierotti
F
F
Peltonen
K
K
D000478:Alkylation; D000818:Animals; D015415:Biomarkers; D002070:Butadienes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004787:Environmental Pollution; D004852:Epoxy Compounds / Q000378:metabolism; D005854:Germ Cells / Q000187:drug effects / Q000378:metabolism; D006147:Guanine / Q000031:analogs & derivatives / Q000032:analysis; D008168:Lung / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009153:Mutagens / Q000378:metabolism / Q000494:pharmacology; D013237:Stereoisomerism; D013737:Testis / Q000737:chemistry / Q000378:metabolism*
D015415:Biomarkers; D002070:Butadienes; D018736:DNA Adducts; D004852:Epoxy Compounds; D009153:Mutagens; C024370:3,4-epoxy-1-butene; D006147:Guanine; C031763:1,3-butadiene